Beyond fear: Patients with posttraumatic stress disorder fail to engage in safety cues

Background For survival, it is crucial to continuously evaluate the presence or absence of risk in the environment. Previously, a safety cue for the observation of aversive pictures attenuated their aversiveness in healthy participants. Here, we investigated whether patients with Posttraumatic Stress Disorder (PTSD) would fail to engage in safety cues using brain reactivity to aversive pictures as a proxy. Methods Patients with PTSD (n = 20) and control participants (n = 23) were exposed to neutral and mutilation pictures. Before the presentation of pictures, a text informed that those were fictitious (“safe context”) or real-life scenes (“real context”); appropriate images were also shown to increase the credibility of the text. A voxel-wise approach identified valence-responsive regions for further testing of an interaction pattern. Results A GROUPxCONTEXTxVALENCE interaction was found in the right supramarginal gyrus spreading anteriorly to the postcentral gyrus - a region involved in the processing of peripersonal space and defensive reactions. Control participants showed, in the real context, increased BOLD response in the right supramarginal gyrus for mutilation pictures compared to neutral ones and, in the safe context, no significant difference between those pictures, indicating an attenuation of brain reactivity. Patients with PTSD presented high brain reactivity in both real and safe contexts. Limitations Patients with PTSD were under pharmacological treatment, and the time posttrauma and comorbidities were not assessed. Conclusions Differently from controls, patients with PTSD did not show attenuation of brain reactivity, reflected by supramarginal response in the safe context. This suggests an inappropriate engagement in safety cues.